This invention relates to a novel process for the preparation of 3-cyclic-ether-substituted cephalosporins. The invention also relates to novel processes for preparing zwitterions, para-nitrobenzyl esters and allyl esters useful in the preparation of the above cephalosporins. The invention also relates to 3-cyclic-ether-substituted cephalosporins. These compounds possess certain advantageous properties, such as crystalline form and high enantiomeric excess (e.e.).
The 3-cyclic-ether-substituted cephalosporins prepared by the methods of the present invention have prolonged and high levels of antibacterial activity and possess good absorption parentally in humans and animals. The 3-cyclic-ether-substituted cephalosporins prepared by the processes of the present invention contain a cyclic ether substituent at carbon 3 of the cephalosporin nucleus.
GB 1405758 describes alternative methods of preparation of certain 3-cyclic-ether-substituted cephalosporins.
J. Antibiotics (1994), vol. 47(2), page 253, and WO 92/01696 also describe alternative methods of preparation of compounds of formula I, as defined herein below, and compounds useful in said processes.
U.S. Pat. Nos. 6,020,329 and 6,077,952 describe salts, polymorphs, solvates and hydrates of 3-cyclic-ether-substituted cephalosporins.
U.S. Pat. No. 6,001,997 describes alternative methods of preparations of 3-cyclic-ether-substituted cephalosporins.
United States Non-Provisional Patent Application entitled “Process and Ester Derivatives Useful For Preparation of Cephalosporins”, filed Dec. 4, 2001, refers to intermediates and processes to prepare 3-cyclic-ether-substituted cephalosporins.
Each of the above referenced publications, patents and patent applications is hereby incorporated by reference in its entirety.
The present inventors have discovered a novel compound of formula I, as defined herein below. The present inventors have also discovered a high-yielding process for the preparation of said compounds of formula I.